The studies are designed to investigate the production of fever in humans by focusing on the small protein, leukocyte pyrogen (LP) which is the mediator of fever. Experiments are concerned with 1) production of LP in immune fever in humans. It has been shown in our laboratory that the antigenic stimulus of the mixed leukocyte reaction results in the release of a lymphokine which, in twins, induces LP synthesis. 2) The ability of neonatal leukocytes to make LP is being investigated in order to study why newborns frequently fail to become febrile with infections. 3) LP, in addition to causing fever by acting on the hypothalamus, also mediates the acute-phase reaction. Data indicate that LP induces in vitro and in vivo SAA synthesis by hepatocytes. We are currently investigating the role of the LP molecule in the pathogenesis by amyloidosis. 4) Basic structure-function studies are being carried-out in order to identify the specific site of action make-up. Using agents which destroy or alter amino acids, we are gathering data which of these are essential to the action of LP in the production of fever.